1. Repetitive head impacts and chronic traumatic encephalopathy are associated with TDP-43 inclusions and hippocampal sclerosis.
- Author
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Nicks R, Clement NF, Alvarez VE, Tripodis Y, Baucom ZH, Huber BR, Mez J, Alosco ML, Aytan N, Cherry JD, Cormier KA, Kubilius C, Mathias R, Svirsky SE, Pothast MJ, Hildebrandt AM, Chung J, Han X, Crary JF, McKee AC, Frosch MP, and Stein TD more...
- Subjects
- Humans, Aged, Aging, DNA-Binding Proteins metabolism, Chronic Traumatic Encephalopathy pathology, Neurodegenerative Diseases, Hippocampal Sclerosis, TDP-43 Proteinopathies pathology
- Abstract
Hippocampal sclerosis (HS) is associated with advanced age as well as transactive response DNA-binding protein with 43 kDa (TDP-43) deposits. Both hippocampal sclerosis and TDP-43 proteinopathy have also been described in chronic traumatic encephalopathy (CTE), a neurodegenerative disease linked to exposure to repetitive head impacts (RHI). However, the prevalence of HS in CTE, the pattern of TDP-43 pathology, and associations of HS and TDP-43 with RHI are unknown. A group of participants with a history of RHI and CTE at autopsy (n = 401) as well as a group with HS-aging without CTE (n = 33) was examined to determine the prevalence of HS and TDP-43 inclusions in CTE and to compare the clinical and pathological features of HS and TDP-43 inclusions in CTE to HS-aging. In CTE, HS was present in 23.4%, and TDP-43 inclusions were present in 43.3% of participants. HS in CTE occurred at a relatively young age (mean 77.0 years) and was associated with a greater number of years of RHI than CTE without HS adjusting for age (p = 0.029). In CTE, TDP-43 inclusions occurred frequently in the frontal cortex and occurred both with and without limbic TDP-43. Additionally, structural equation modeling demonstrated that RHI exposure years were associated with hippocampal TDP-43 inclusions (p < 0.001) through increased CTE stage (p < 0.001). Overall, RHI and the development of CTE pathology may contribute to TDP-43 deposition and hippocampal sclerosis., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.) more...
- Published
- 2023
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